Cytochrome c oxidase, the terminal enzyme of the respiratorychain, is a membrane protein located in the inner membrane ofmitochondria and the plasma membrane of prokaryotes. It accepts electrons from cytochrome c and uses them to reduce oxygen to water at the copper-iron binuclear center.Coupled tothe redox reaction, protons are transfered across the membrane,creating a gradient that is used elsewhere, for instance in the synthesis of ATP. Although crystal structures for two cytochrome coxidases were reported last summer [8, 61], the mechanism ofproton pumping remains unclear. Internal waters are essential for proton pathways, but cannot beresolved in the crystal structure.Using a method developed inJan Hermans group at UNC [62] we were able to find over ahundred likely water sites in the X-ray structure provided byH. Michel.The placed waters clearly confirm the existence oftwo proton channels proposed previously. We have also started molecular dynamics simulations on a 16,000atom subset of the protein. The calculations are carried out fordifferent stages of the reaction cycle using X-PLOR and recently NAMD. During the simulations polar residues and waters in theproton channels form highly ordered hydrogen bond chains andnetworks, whose polarization depends critically on the redox stateof the binuclear center.Proton conduction is thereby coupledto the state of the reaction center.This is a first step towardsunderstanding the mechanism of the proton pump.